Functional Immunoaffinity 3D Magnetic Core–Shell\nNanometallic Structure for High-Efficiency Separation and Label-Free\nSERS Detection of Exosomes

Tumor\nexosomes, known as maternal cell messengers, play an important\nrole in cancer occurrence, proliferation, metastasis, immune escape,\ndrug resistance, and other processes and are an entry point for cancer\nresearch. However, there is still a lack of an efficient detection\ntechnology for exosomes. In this study, the ultrahigh sensitivity\nSERS nanoprobe with a three dimensional (3D) magnetic core/Au nanocolumn/Au\nnanoparticles shell strongly coupling multistage structure (Fe<sub>3</sub>O<sub>4</sub>@NR-NPs) was constructed by crystal growth of\nnanocrystals in the confined space of a central radiating single particle\nmesoporous molecular sieve channel and strong coupling secondary growth\nof gold particles. The exosomes were confined onto the “hot\nspot” of plasmonic nanoparticles and rapidly enriched by CD63\nantibody functional-Fe<sub>3</sub>O<sub>4</sub>@NR-NPs to achieve\nhigh sensitivity detection, with the limit of detection of 1 ×\n10<sup>3</sup> particles/mL (S/N = 3). The spectral data set of different\nexosomes is applied to train for multivariate classification of cell\ntypes and to estimate how the normal exosome data resemble cancer\ncell exosomes by principal component analysis (PCA). Finally, this\ndetection method has also been successfully employed for the detection\nof exosomes in complex samples; this proves that the proposed SERS-based\nmethod is a promising tool for clinical cancer screening.